Case studies and reviews of Lyme disease describing how this vector-borne infection manifests in some patients as scleroderma in its various systemic and limited forms, as well as other connective tissue diseases.
Diagnostic and Treatment Strategies of Dermatologists for Treating Morphea in Hungary. Acta Dermatovenerol Croat. 2018 Apr;26(1):21-24.
Researchers in the Dermatology Department of Semmelweis University in Budapest, Hungary, developed a questionnaire that was sent to Hungarian dermatologists to determine the diagnostic and treatment strategies employed for morphea patients. Four-fifths of 101 respondents replied that they tested for Lyme disease (a tick-borne infection that has been strongly correlated with morphea in evidence-based scientific literature – see below), and although topical steroid preparations were commonly-used for skin lesions, most doctors in the clinical setting preferred antibiotic therapy (either doxycycline or penicillin) for systemic treatment (presumably for the triggering infection). As only a small percentage (6.9%) of doctors in Hungary responded that they use the immune-suppressant, methotrexate, these study authors expressed the need for universal diagnostic and treatment guidelines for morphea, referring to those employed in western nations that recommend the use of systemic steroids and methotrexate.
Clinical pathologic correlations of Lyme disease by stage. Ann N Y Acad Sci. 1988;539:65-79
Report describing the immunologic damage caused by late stage manifestations of Lyme, suggestive of collagen-vascular diseases, such as scleroderma, lupus, polymyositis, and dermatomyositis, as seen on histologic examination of tissue samples. Dr. Alan Steere (rheumatologist) and Dr. Paul Duray (pathologist) suggest that this type of damage is in response to persistence of the causative organism of Lyme disease, a spirochete, called Borrelia burgdorferi (Bb), “… however few in number.”
Acute exacerbation of systemic scleroderma in Borrelia burgdorferi infection. Journal of the European Academy of Dermatology & Venereology, Volume 19, Number 1, January 2005, pp. 93-96(4)
Case of 61-year-old woman with swift onset, seropositive systemic scleroderma, testing positive for Borrelia burgdorferi sensu lato, treated with intravenous ceftriaxone, leading to successful resolution of skin stiffness and induration within two weeks. Authors conclude that in atypical cases of skin sclerosis that Lyme disease should be considered when there is a predisposition to developing systemic scleroderma.
Heterogeneity of Borrelia burgdorferi in the skin. Am J Dermatopathol. 1996 Dec;18(6):571-9.
Lyme spirochetes and atypical forms of the microbe were found in skin biopsies of patients with morphea, acrodermatitis chronica atrophicans (ACA), and cultured from the classic bulls-eye Lyme rash, called erythema chronicum migrans (ECM). The spirochetal forms identified in tissue biopsies were identical to those found in a model of borrelia-injected skin and also found in cultured samples exposed to hyperimmune sera and/or antibiotics. This study demonstrates not only that Lyme spirochetes may be found in morphea skin plaques, but that atypical morphologic (altered or variable) forms of borrelia burgdorferi (Bb) may also be present.
Positive IgG Western blot for Borrelia burgdorferi in Colombia. Mem Inst Oswaldo Cruz. 1999 Jul-Aug;94(4):499-503.
Serum samples of 20 patients with dermatologic (and other) signs of Lyme disease, including two with localized scleroderma that were found to be seropositive for the infection on IgG western blot testing by CDC criteria, in Cali, Columbia. The authors suggest the potential of a Lyme-like infection that might produce positive IgG results on standard western blot testing that is caused by a spirochete genospecies that is distinct from either Borrelia burgdorferi senu stricto or Borrelia burgdorferi sensu lato. The study authors call for testing of tick populations in the region to seek evidence of a Borrelia variant.
Evidence for Borrelia burgdorferi in morphea and lichen sclerosus. Int J Dermatol. 2000 Apr;39(4):278-83.
Turkish researchers identified Borrelia burgdorferi DNA in 3/10 morphea and 6/12 lichen sclerosis patients, stating that it may play a role in the etiopathogenesis of both skin diseases in western parts of Turkey.
[Borrelia burgdorferi antibodies in scleroderma circumscripta, lichen sclerosus et atrophicus, erythema nodosum, granuloma annulare, erythema annulare and chronic urticaria]. Bratisl Lek Listy. 2000;101(4):194-9.
Borrelia burgdorferi found in high antibody titers in 34.4% of scleroderma circumscripta patients and other dermal diseases and authors suggest that Lyme may play a role in disease etiology of each of the study groups.
Chronic borreliosis presenting with morphea- and lichen sclerosus et atrophicus-like cutaneous lesions. a case report. Dermatology. 2001;202(4):373-5.
Case of Lyme disease presenting with dermal features of acrodermatitis chronica atrophicans (ACA) that are compatible with morphea and lichen sclerosus et atrophicus and that fall in the spectrum of dermal diseases associated with chronic borrelia burgdorferi infection.
The outcome of Lyme borreliosis in children. Wien Klin Wochenschr. 1999 Dec 10;111(22-23):941-4.
A study of 36 Austrian children (one with circumscribed scleroderma and one with acrodermatitis chronica atrophicans) was to determine if the high seroprevalence of Lyme (13%) in healthy blood donors was the result of infection during childhood. Of note is that 25% of the children did not have a classic erythema migrans (EM) rash and only 64% were IgM positive and only 44% IgG positive (prior to antibiotic treatment for 3-4 weeks) for Lyme. Also of note is that, post-treatment, some children experienced persistent symptoms and that some, with or without symptoms, remained seropositive for Lyme past one year. The authors conclude with the assumption that recurrent, often silent, Lyme infections might increase antibody titers, over time, and with age.
“Borrelia-associated early-onset morphea”: a particular type of scleroderma in childhood and adolescence with high titer antinuclear antibodies? Results of a cohort analysis and presentation of three cases. J Am Acad Dermatol. DOI: http://dx.doi.org/10.1016/j.jaad.2008.09.023
Study demonstrating that early-onset morphea may be induced by borrelia burgdorferi infection. German and Hungarian researchers state that this autoimmune phenomenon is characterized by high-titer antinuclear antibodies (ANA) and a particularly severe disease course, requiring treatment of the infection and skin inflammation.
Parry-Romberg syndrome: a possible association with borreliosis. J Eur Acad Dermatol Venereol. 2004 Mar;18(2):204-7.
Case of woman with Parry-Romberg syndrome, coincident with Lyme disease. This condition shares some features with linear scleroderma, ‘en coup de sabre,’ but is distinguished by the lower hemi-facial atrophy and dermal sclerosis with either childhood or early adult onset. Study authors hypothesize that the cause of Parry-Romberg syndrome may involve borreliosis.
Localized scleroderma unius lateri and Borrelia burgdoferi infection. Indian J Dermatol Venereol Leprol. 2012 May-Jun;78(3):383-5. doi: 10.4103/0378-6323.95460.
Case of 27-year-old Moroccan male, previously living in Italy for 10 years, and seropositive for Lyme and localized scleroderma, was treated with intramuscular benzathine penicillin for two treatment cycles of 20 days, after which significant improvement of skin plaques were noted.
[Clinical picture of Lyme boreliosis] Wiad Parazytol. 1999;45(2):143-9.
Article (1999), describing the high prevalence of Lyme and its broad spectrum of disease manifestations in Poland, including morphea sclerodermatous skin lesions, acrodermatitis chronica atrophicans, arthritis, facial palsy, borrelial lymphocytoma, lymphocytic meningitis, cardiac transduction disturbances, cardiomyopathy, and neurological disorders. Authors cast doubt on laboratory testing for borreliosis and state that diagnosis must be based on typical signs of the disease.
The expanding spectrum of cutaneous borreliosis. G Ital Dermatol Venereol. 2009 Apr;144(2):157-71.
Discussion of the wide and variable spectrum of cutaneous borreliosis, including morphea, lichen sclerosis, acrodermatitis chronica atrophicans, cutaneous B-cell lymphoma, cutaneous sarcoidosis, necrobiosis lipoidica, necrobiotic xanthogranuloma, granuloma annulare, interstitial granulomatous dermatitis, erythema annulare centrifugum or lymphocytic infiltration (Jessner Kanof) of the skin. The spectrum of potential cutaneous borreliosis manifestations is described by the authors as, “the chameleon of dermatology.”
[A late revealing of a case of tick-born borreliosis]. Klin Med (Mosk). 2007;85(8):70-1.
Based on earlier reports of a firm etiopathogenic association of Lyme disease with morphea scleroderma, the confirmed diagnosis of a case of limited scleroderma, caused by borrelisois, was made possible in Russia, based on lab testing, clinical signs and symptoms, and epidemiological data.
Morphoea: a manifestation of infection with Borrelia species? Br J Dermatol. 2007 Dec;157(6):1189-98. Epub 2007 Oct 17.
In 84 of 122 cases (68.9%) of morphea, a high prevalence of borrelia was detected in tissue samples using focus floating microscopy (FFM). Positive results were more frequent (75%) in early inflammatory lesions than in late inflammatory-poor (53%) and live organisms found more frequently at the borders than in the fibrosclerotic portions of the lesions with FFM testing. On the other hand, PCR testing detected only 1 of 30 cases of borrelia infection in morphea lesions analyzed. Authors state that FFM tissue testing is a highly sensitive method of borrelia detection in morphea and provides significant evidence for this infection, or similar strains, as being a trigger for the disease.
A Morphealike Skin Condition Caused by Borrelia burgdorferi in an Immunocompromised Patient. Mayo Clin Proc. 2006 Sep;81(9):1259-60, 1263.
Case of a 66-year-old American woman, with chronic lymphocyctic leukemia, receiving chemotherapy, developed a morphea-like skin condition. Immuno-incompetent and unable to test positive on standard indirect ELISA or western blot antibody testing, the patient was proven to have Lyme disease upon testing of cultured tissue samples, by polymerase chain reaction (PCR) and borreliacidal antibody test (BAT). Treatment with doxycycline was able to clear the lesions.
Lymphoproliferative responses to Borrelia burgdorferi in circumscribed scleroderma. Br J Dermatol. 1996 Feb;134(2):285-91.
Lymphocytic response to borrelia infection was tested in patients with circumscribed scleroderma, other disease manifestations of Lyme, and healthy volunteers exposed to Lyme for 5 days, acting as controls. Test results demonstrated that study participants, including seropositive or seronegative circumscribed scleroderma patients, had elevated borrelia-induced lymphocytic-proliferation. Also, that the magnitude of lymphocytic responses to the infection was comparable between subjects with circumscribed scleroderma and other disease manifestations, and that antibiotic therapy can significantly ameliorate this humoral response. Authors conclude that Lyme may be a causative agent of circumscribed scleroderma in some cases, whether seropositive or not for the infection, and urge the import of conducting lymphocytic function assays, especially in patients with negative Lyme serology.
[The dermatologic spectrum of Lyme borreliosis]. Wien Med Wochenschr. 1995;145(7-8):165-70.
Discussion of the typical and atypical dermal presentations of Lyme disease. Atypical presentations that can be clinically diagnosed, include erythema migrans, borrelia lymphocytoma and acrodermatitis and chronica atrophicans (ACA). However, atypical Lyme dermatoses, diagnosed by skin biopsy culture, include, dermatoses of unknown origin, such as circumscribed scleroderma, dermatomyositis-like syndrome, relapsing nodular panniculitis, granuloma anulare, and roseolar erythemas. The author recommends new standardized diagnostic procedures to define the spectrum of skin diseases caused by Lyme disease and that new therapeutic antibiotic strategies have proven to be successful in treating these dermal manifestations.
A Painful Inflammatory Lesion on the Dorsum of the Hand of a Patient With Rheumatoid Arthritis Treated With Methotrexate. Clin Infect Dis (2014) 59 (6): 903.
The case of an elderly woman with rheumatoid arthritis, treated with methotrexate, who developed an Acrodermatitis chronica atrophicans (ACA) lesion on the dorsal side of her hand. ACA is a known skin manifestation of late stage Lyme disease, occurring months to years after infection, and can resemble morphea scleroderma lesions. Although the patient couldn’t recall a tick bite, she was found positive for Lyme disease and treated with IV ceftriaxone, which resulted in ACA resolution. While ACA can also present with peripheral neuropathy, lymphadenopathy and fibrotic nodules over joints can lead to misdiagnosis. The authors conclude by stating, “…we cannot exclude that long-term methotrexate treatment and the history of axillary lymph node dissection may have induced this late local dissemination.”
Lyme disease: musculoskeletal manifestations. Rheum Dis Clin North Am. 1989 Nov;15(4):649-56.
In this commentary by the Section of Rheumatology, University of Minnesota School of Medicine, Minneapolis, the authors state that Lyme disease, while closely resembling reactive arthropies, it has also mimicked other connective tissue disorders, such as juvenile rheumatoid arthritis, rheumatoid arthritis, myositis, and scleroderma.
Borrelia burgdorferi Infections in the United States.
Extensive review of the prevalence of Lyme disease in the US and other parts of the world, and a discussion on the dermatologic presentations of Lyme, including localized forms of morphea scleroderma. The authors state that borrelia burgdorferi organisms are collagenotrophic, having a preference for collagen-rich tissues, and that histologic examination of morphea skin biopsies revealing these microbes suggest, “… the role of B. burgdorferi in the onset of morphea is thought to be related to the inflammatory and immune processes elicited by the presence of the spiral organism within the patient’s tissues.”